Gene Expression Profiles of the Immuno-Transcriptome in Equine Asthma

Simple Summary The clinical importance and the great economic impact of equine asthma (EA), classified as mild (MEA) and severe (SEA), have led to several studies to better understand its features; however, the fragmented information available does not allow researchers to fully describe the pathophysiology of this disease. Transcriptomic analysis can help in understanding the biological mechanisms underlying equine asthma. To date, the great majority of gene expression studies on equine airway diseases have focused on the analysis of only a few candidate genes, hampering robust conclusions about EA pathogenesis. In the present study, the employment of an immune-specific horse array on SEA and MEA-affected horses helped to comprehensively define their transcriptomic fingerprints. For both diseases, findings suggest that the increased amount of mucus in the airways is due to mucociliary clearance reduction rather than mucus hypersecretion. In addition, excessive complement activation might be responsible for tissue injury. Other biological pathways, mainly those involved in the perpetuation of chronic inflammation and tissue remodeling similar to human asthma, are characteristic of SEA. Background: Mild equine asthma (MEA) and severe equine asthma (SEA) are two of the most frequent equine airway inflammatory diseases, but knowledge about their pathogenesis is limited. The goal of this study was to investigate gene expression differences in the respiratory tract of MEA- and SEA-affected horses and their relationship with clinical signs. Methods: Clinical examination and endoscopy were performed in 8 SEA- and 10 MEA-affected horses and 7 healthy controls. Cytological and microbiological analyses of bronchoalveolar lavage (BAL) fluid were performed. Gene expression profiling of BAL fluid was performed by means of a custom oligo-DNA microarray. Results: In both MEA and SEA, genes involved in the genesis, length, and motility of respiratory epithelium cilia were downregulated. In MEA, a significant overexpression for genes encoding inflammatory mediators was observed. In SEA, transcripts involved in bronchoconstriction, apoptosis, and hypoxia pathways were significantly upregulated, while genes involved in the formation of the protective muco-protein film were underexpressed. The SEA group also showed enrichment of gene networks activated during human asthma. Conclusions: The present study provides new insight into equine asthma pathogenesis, representing the first step in transcriptomic analysis to improve diagnostic and therapeutic approaches for this respiratory disease.